Inge-Vechtomov S G
Ontogenez. 2011 Sep-Oct;42(5):337-45.
Several neurodegenerative diseases (so-called age-related diseases) in humans are associated with development of protein aggregates--amyloids. Prion diseases--kuru, Kreutzfeldt-Jakob and Gerstmann-Straussler-Sheinker diseases, fatal familial insomnia, etc.--are examples of infectious amyloidoses. A model system for investigation of mechanisms of amyloidogenesis and of its infectious nature had been developed as a result of yeast prion discovery. The existence of a prion network as an interaction of different prions identified in yeast is being confirmed recently as an interaction of different anyloids in humans. The potential danger of amyloidoses is conditioned by the very structure of almost all proteins containing fragments capable to be organized as beta-sheets, which lead to their aggregation being exposed. Meanwhile, there are several well-defined examples of the adaptive value of amyloid aggregates: cytoplasmic incompatibility factor in Podospora anserina, spider silk, cytoplasmic stress granules in mammals, prion form of CPEB protein responsible for the neuron activity in Aplisia, etc. These facts should be taken into consideration when seeking antiamyloid drugs. Discovery of protein inheritance in lower eukaryotes modifies our knowledge of the template principle significance in biology and adds a concept of conformational templates (II order templates) involved in reproduction of the three-dimensional structure of the supramolecular complexes in the cell.
人类的几种神经退行性疾病（即所谓的年龄相关性疾病）与蛋白质聚集体——淀粉样蛋白的形成有关。朊病毒疾病——库鲁病、克雅氏病、格斯特曼-施特劳斯勒-谢克尔病、致死性家族性失眠症等——都是传染性淀粉样变性的例子。酵母朊病毒的发现促成了一个用于研究淀粉样蛋白生成机制及其传染性本质的模型系统的建立。最近证实，酵母中鉴定出的不同朊病毒之间的相互作用所构成的朊病毒网络，与人类中不同淀粉样蛋白之间的相互作用类似。淀粉样变性的潜在危险取决于几乎所有含有能够形成β折叠片段的蛋白质的结构，这些片段暴露后会导致蛋白质聚集。与此同时，也有几个明确的例子表明淀粉样聚集体具有适应性价值：如粪生粪壳菌中的细胞质不相容因子、蜘蛛丝、哺乳动物中的细胞质应激颗粒、负责海兔神经元活动的CPEB蛋白的朊病毒形式等。在寻找抗淀粉样蛋白药物时，应考虑到这些事实。低等真核生物中蛋白质遗传的发现改变了我们对模板原理在生物学中重要性的认识，并引入了构象模板（二级模板）的概念，该概念涉及细胞中超分子复合物三维结构的复制。
